DESCRIPTION: (Applicant Abstract) A common result of prolonged alcohol consumption is liver damage. There is a considerable body of evidence that implicates the first metabolite of ethanol oxidation, acetaldehyde. and malondialdehyde as the precursors to hepatotoxicity. When hepatic proteins are incubated with both aldehydes, hybrid protein adducts are generated. At long reaction times the adducts are highly fluorescent while non-fluorescent adducts predominate at the early stages of reaction. It has been determined that the structure of the fluorescent adduct is a 1,4-dihydopyridine 3,5-dicarboxaldehyde, formed by a Hantzsch reaction of acetaldehyde, malondialdehyde, and the epsilon amino group of a lysine residue. Recent evidence indicates that the structure of the non-fluorescent adduct is a 2-formyl-3-alkylamino-butanol. The research proposed here will focus on two areas. One project is aimed at identifying the conditions necessary for formation of the these adducts. This will involve monitoring the reaction between acetaldehyde, malondialdehyde, and small peptides by nuclear magnetic resonance (NMR) and fluorescence spectroscopy. The peptides will have lysine residues sandwiched between various amino acids in order to identify local environments which enhance the production of one or both adducts. The second project is aimed at clarifying the reaction mechanism which accounts for the formation of the non-fluorescent adduct. The reaction between acetaldehyde, malondialdehyde, and a primary amine will monitored by NMR to determine the structures of any intermediate species.